2-229553710-T-G

Variant names:

• chr2-229553710-T-G
• rs1477111
• NM_139072.4:c.848-6618A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139072.4(DNER):​c.848-6618A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,100 control chromosomes in the GnomAD database, including 47,852 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (47852 hom., cov: 31)
• Consequence: DNER NM_139072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55

Genes affected

DNER (HGNC:24456): (delta/notch like EGF repeat containing) Predicted to enable Notch binding activity. Involved in central nervous system development. Located in dendrite; early endosome; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNER	NM_139072.4	c.848-6618A>C		intron_variant	Intron 4 of 12	ENST00000341772.5	NP_620711.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNER	ENST00000341772.5	c.848-6618A>C		intron_variant	Intron 4 of 12	1	NM_139072.4	ENSP00000345229.4

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120232 AN: 151982 Hom.: 47790 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.815

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.791 AC: 120356 AN: 152100 Hom.: 47852 Cov.: 31 AF XY: 0.794 AC XY: 59034 AN XY: 74362

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.809

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.815

Alfa AF: 0.775 Hom.: 64410

Bravo AF: 0.801

Asia WGS AF: 0.861 AC: 2995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1477111; hg19: chr2-230418426;